Abstract
One-Year Follow-Up of Feasibility and Safety of the First U.S., Randomized, Controlled Study Using 3-Dimensional Guided Catheter-Based Delivery of Autologous Skeletal Myoblasts for Ischemic Cardiomyopathy (CAuSMIC Study)
Nabil Dib, Jonathan Dinsmore, Zaki Lababidi, Bee White, Susan Moravec, Ann Campbell, Amy Rosenbaum, Katayoun Seyedmadani, Wael A. Jaber, Craig S. Rizenhour, Edward Diethrich
A Phase-1 clinical trial was conducted to evaluate the safety and feasibility of myoblast transplantation with the Biosense-NOGA (Diamond Bar, California) 3-dimensional-guided endomyocardial delivery system. Twenty-three subjects with previous myocardial infarction and symptoms of heart failure, New York Heart Association (NYHA) functional class II to IV (11 control and 12 treated subjects), were enrolled. Treated subjects showed sustained improvements in NYHA (p < 0.0004) and Minnesota Living with Heart Failure Questionnaire compared with control subjects (p = 0.004). Blinded core laboratory echocardiography evaluations showed evidence for reductions in treatment versus control in end diastolic diameter (p = 0.07) and end systolic diameter (p = 0.07). This trial demonstrated safety and feasibility and warrants initiation of larger efficacy studies.
The aim of this study was to test safety and feasibility of myoblast transplantation with the Biosense-NOGA (Diamond Bar, California) 3-dimensional-guided endomyocardial delivery system.
Previous Phase-1 trials showed feasibility of epicardial injection of myoblasts. However, catheter-based delivery has several advantages: it can be applied on high-risk patients, the procedure can be repeated, and it is associated with less morbidity and mortality.
Twenty-three subjects, with previous myocardial infarction and heart failure, New York Heart Association (NYHA) functional class II to IV, were enrolled, 11 control and 12 treatment subjects. To assess safety, physical exam, electrocardiogram, continuous rhythm monitoring, quality of life assessments, and heart function were evaluated at baseline and follow-up until 1 year.
There was favorable safety: no difference between groups in arrhythmias, and no deaths. Treated subjects showed sustained improvements in NYHA and Minnesota Living with Heart Failure Questionnaire (MLHFQ) compared with control subjects (NYHA, −1.0 point in treatment vs. +0.3 point in control group, p < 0.0004; MLHFQ, −14 point in treatment vs. +1 point in the control group, p = 0.004). Blinded core laboratory echocardiography evaluations showed sustained reductions in the treatment versus control in end diastolic diameter (−0.03 cm vs. +0.05 cm, p = 0.07) and end systolic diameter (−0.05 cm vs. +0.1 cm, p = 0.07). Finally, NOGA voltage mapping demonstrated improved voltage measurements (+1.0 mV, p = 0.008).
This trial of myoblast transplantation via catheter into heart failure patients demonstrated safety and feasibility. Treated patients showed improvement in NYHA, MLHFQ, ventricular viability, and evidence of reverse ventricular remodeling. These data demonstrate positive safety outcomes and warrant initiation of larger phase 2, double-blind, placebo-controlled clinical trials.